VSV infection ameliorates autoimmune disease in FcγR2B deficient mice (101.14)

Abstract We have investigated whether infection by pathogens affects the development of autoimmune diseases such as lupus. We tested the effect of infection with vesicular stomatitis virus (VSV) on two mouse strains that spontaneously develop lupus disease. Infection of VSV in lupus prone FcγR2B-/- (R2) mice significantly reduced autoantibody titers and inflammatory cytokines and chemokines in serum, reduced glomerulonephritis, and improved survival. In contrast, VSV infection in R2yaa mice, which develop a more aggressive lupus disease, showed slightly reduced auto-antibody titers in the serum without any major changes in serum cytokines and chemokines, kidney glomreulonephritis, or survival. Characterization of immune cell phenotypes in VSV infected R2 mice showed that B cell development in the bone marrow was not affected whereas germinal center, plasma, and IgG producing mature B cell numbers were reduced. Additionally, VSV infected R2 mice had lower number of follicular helper T cells and CD11c+ cells in the spleen. Compared to uninfected mice, microarray analysis of naïve resting B cells from VSV infected R2 splenocytes showed up-regulation of several candidate genes including a non receptor type protein tyrosine phosphatase, PTPN22 that has been shown to be associated with Lupus and other autoimmune diseases. Studies of the functional implications of Ptpn22 overexpression in VSV-infected R2 B cells are in progress.